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BLACKCEDAR PHARMACEUTICALS LTD.

PIONEERING THE CHANGE IN HYPERTENSION

THERAPY IN NIGERIA WITH

BICEDOLOL® Bisoprolol Fumarate 5mg & Hydrochlorothiazide 6.25mg

HIGH EFFICACY - LOW DOSAGE

With low-dose combination therapy BICEDOLOL® provides classic

antihypertensive benefits of beta-blockers and diuretics without their dose-

related side effects.



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TABLE OF CONTENT DRUG EVALUATION & RESEARCH RECOMMENDATION ...................................................................... 3

FIRST LINE TREATMENT IN HYPERTENSION ........................................................................................ 4

CLINICAL TRIALS ................................................................................................................................... 5

RESPONSE RATE UP TO 73% ................................................................................................................ 6

ADVERSE EVENTS COMPARABLE TO PLACEBO .................................................................................... 7

REDUCTION IN DIASTOLIC BLOOD PRESSURE ..................................................................................... 8

REDUCTION IN SYSTOLIC BLOOD PRESSURE ....................................................................................... 9

RESPONSE & SAFETY PROFILE VS. ACE INHIBITORS & CA-ANTAGONISTS ......................................... 10

LOWEST DISCONTINUATION RATES .................................................................................................. 11

EFFICACY REGARDLESS OF AGE, RACE OR GENDER .......................................................................... 12

NOTIFICATION DELIVERED BY NAFDAC ............................................................................................. 13

ABSTRACTS ........................................................................................................................................ 14

ABSTRACTS ........................................................................................................................................ 15

ABSTRACTS ........................................................................................................................................ 16

ABSTRACTS ........................................................................................................................................ 17

REFERENCES ...................................................................................................................................... 18

CONTACTS ......................................................................................................................................... 19



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DRUG EVALUATION & RESEARCH RECOMMENDATION



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FIRST LINE TREATMENT IN HYPERTENSION BICEDOLOL® is recommended by Drug Evaluation and Research (DER) and approved by NAFDAC for

the treatment of mild to moderate essential hypertension.

The combination & dosage in BICEDOLOL® is Recommended as a first line treatment in hypertension

by the American Joint National Committee on Prevention, Detection, Evaluation & Treatment of High

Blood Pressure.

It is recommended by NAFDAC’s Drug Evaluation & Research Unit for the treatment of mild to

moderate essential hypertension.

BLACKCEDAR PHARMACEUTICALS LTD is pioneering this change in Hypertension therapy in Nigeria

with BICEDOLOL®.

BICEDOLOL® was approved by NAFDAC in December 2014 for the treatment of hypertension.

HIGH EFFICACY Control of hypertension in up to 84% of patients

Effective in a broad range of patients regardless of age,

race or gender

Recommended by the JNC VI and other guidelines

Approved by NAFDAC as treatment of mild to moderate

essential hypertension

Approved by the FDA as first-line treatment of

hypertension

LOW RATE OF ADVERSE EVENTS Low-dose drug

Specifically developed to minimize dose-related side

effects

Side-effect profile comparable to placebo

MULTI-ACTIVE MODE OF ACTION Additive antihypertensive efficacy

Blood pressure reduction via different mechanisms

Metabolically neutral

IMPROVED COMPLIANCE Improvement in quality of life

Once-daily dosage (consistent 24 hour-efficacy)

Low discontinuation rates

Changes in Hypertension Therapy

Basic antihypertensive therapy with

high efficacy & low side effects

BICEDOLOL®



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CLINICAL TRIALS

The US National Hypertension Trial with 12’629 patients confirmed positive data of BICEDOLOL®

(Bisoprolol Fumarate 5mg + HCTZ 6.25 mg) regarding efficacy, side-effects profile and quality of life in

actual clinical practice under usual care conditions.

Frishman et al, 1994-

Benetos et al, 2000 - 164

Papademetriou et al, 1998 - 75Neutel et al, 1996 -

Frishman et al,

Prisant et al , 1995 -

RANDOMIZED, DOUBLE BLIND TRIALS

Frishman et al , 1994 Benetos et al, 2000 Papademetriou et al, 1998

Neutel et al, 1996 Frishman et al , 1995 Prisant et al , 1995



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RESPONSE RATE UP TO 73%

Response rate for BICEDOLOL® is up to 73%.

Other antihypertensive monosubstances will require much higher dosages to achieve similar

results in terms of response rate.

BICEDOLOL® and traditional dosage combinations are equivalent in terms of response rate

BUT with additional advantage.

LOW SIDE EFFECTS BECAUSE OF THE LOW DOSAGES OF THE TWO ACTIVE SUBSTANCES

Response rate is defined as a sitting diastolic blood pressure of ≤ 90mm Hg and or decrease

from baseline of ≥10mm Hg measured 24hours after dosing.

Bicedolol, 73%

Placebo, 27%

HCTZ 25mg, 44%

Traditional combination, 78%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

Bicedolol

Placebo

HCTZ 25mg

Traditional combination

RESPONSE RATE OF BICEDOLOL VS. MONODOSE & PLACEBO



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ADVERSE EVENTS COMPARABLE TO PLACEBO

In all clinical trials including more than 14’000 patients BICEDOLOL® (Bisoprolol Fumarate 5mg

+ HCTZ 6.25mg) demonstrated a side-effect profile comparable to placebo on a minimum level.

0% 2% 4% 6% 8% 10% 12%

Bicedolol

Placebo

INCIDENCE OF ADVERSE EVENTSBICEDOLOL VS. PLACEBO

Rash Cough Diarrhea Bradycardia Dyspepsia Nausea Dizziness Asthenia Edema Headache



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REDUCTION IN DIASTOLIC BLOOD PRESSURE

Therapy with BICEDOLOL® produced significant reductions from baseline sitting diastolic blood

pressure than placebo.

The mean reduction in SiDBP was also greater for patients taking BICEDOLOL® versus HCTZ alone in

a much higher dosage.

The low-dosed antihypertensive therapy with BICEDOLOL® results in a strong blood pressure

reduction with a side-effect profile comparable to placebo.

12.6

3.9

10.9

8.4 8.4

0

2

4

6

8

10

12

14

1

REDUCTION FROM BASELINE DIASTOLIC PRESSURE (mm Hg)

Bicedolol Placebo Bisoprolol 10mg Bisoprolol 2.5mg HCTZ 25mg



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REDUCTION IN SYSTOLIC BLOOD PRESSURE

Therapy with BICEDOLOL® produced significant reductions from baseline sitting systolic blood

pressure than placebo.

The mean reduction in SiSBP was also greater for patients taking BICEDOLOL® versus HCTZ alone in

a comparable dosages.

The low-dosed antihypertensive therapy with BICEDOLOL® results in a strong blood pressure

reduction with a side-effect profile comparable to placebo.

-15.8

-2.9

-12.6 -12.6

-9-8.4

-6.2

-18

-16

-14

-12

-10

-8

-6

-4

-2

0

1

EFFECTIVE REDUCTION IN SYSTOLIC BLOOD PRESSURE (mm Hg)

Bicedolol Placebo Bisoprolol 10mg Bisoprolol 40mg Bisoprolol 2.5mg HCTZ 25mg HCTZ 6.25



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RESPONSE & SAFETY PROFILE VS. ACE INHIBITORS & CA-ANTAGONISTS

0% 10% 20% 30% 40% 50% 60% 70% 80%

Bicedolol

Amlodipine

Enalapril

Placebo

RESPONSE VS. ACE INHIBITORS & CA-ANTAGONISTS

23.5%

27.9%

25.3%

26.6%

21.0%

22.0%

23.0%

24.0%

25.0%

26.0%

27.0%

28.0%

29.0%

1

EXCELLENT SAFETY PROFILE FOR BICEDOLOL

Bicedolol Amlodipine Enalapril Placebo



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LOWEST DISCONTINUATION RATES

Discontinuation rates for BICEDOLOL® were lowest in comparative studies vs Amlodipine, Enalapril

and placebo due to adverse events, lack of efficacy (Blood Pressure not controlled) as well as due to

other reasons.

A total of only 16.6% of patients who were treated with BICEDOLOL® discontinued therapy, 26.6% of

patients under Amlopdipine and 26.1% patiens under Enalpril.

Placebo treatment resulted in a discontinuation rate of 58.2%,including 41.8% due to lack of efficacy

(Neutel et al., 1996)

Discontinuation rates for BICEDOLOL® were also lower compared to ACE inhibitors due to adverse

events 7.1% for BICEDOLOL® vs. 9.5% for ACE inhibitors, due to lack of efficacy 2.7% vs. 5.6% and due

to administrative and other reasons 16.7% vs. 17.9%, in total 26.5% vs. 33.0% (Frishman, 1996)

0.0% 5.0% 10.0% 15.0% 20.0% 25.0% 30.0% 35.0% 40.0% 45.0%

Adverse Event

Lack of Efficiency

Others

LOWEST DISCONTINUATION RATE FOR BICEDOLOL

Placebo Enalapril Amlodipine Bicedolol



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EFFICACY REGARDLESS OF AGE, RACE OR GENDER

AGE: BICEDOLOL® allows low-dose therapy in elderly patients, who are paricularly sensitive to the

effects of blood pressure manipulation and medication side effects as a result of the physiological

changs due to aging. Thus all age-groups may benefit from the low incidence of side effects of

BICEDOLOL®

RACE: BICEDOLOL® addresses the physiological mechanism of hypertension (low renin and volume

expansion) common among the black population, and therefore produces effects which are as high

as those observed in non-black population.

73%69%

81%

64%

86%

75% 73%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1

SIGNIFICANT EFFICACY REGARDLESS OF AGE, RACE OR GENDER

All patients <60 years >60 years Male Female Black Non Black



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NOTIFICATION DELIVERED BY NAFDAC



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ABSTRACTS J Natl Med Assoc. 1996 Mar; 88(3):171-5. Saunders E1, Neutel J.

A new antihypertensive strategy for black patients: low-dose multi-mechanism therapy.

Abstract: Hypertension poses serious health risks for blacks because this population presents with earlier onset and more

severe forms of the disease than do nonblack. Although diuretics are the cornerstone of antihypertensive therapy In the

black population, investigators have expressed concern about adverse metabolic effects, such as hypokalaemia, produced

by the high doses of diuretics traditionally prescribed for blacks.

Recent evidence suggests that black patients may respond equally well to the new generation of cardio selective beta-

blockers and angiotensin-converting enzyme inhibitors, particularly when these agents are used together with a diuretic.

A new low-dose multi-mechanism agent that combines the cardio selective beta-blocker Bisoprolol Fumarate with

hydrochlorothiazide, a benzothiazine diuretic, is now available for first-line therapy for hypertension.

Results of two US multicentre trials--including a subset analysis of black patients--indicate that the once-daily agent is highly

effective in reducing diastolic and systolic blood pressure throughout a 24-hour period in both black and nonblack patients.

The agent is well tolerated in blacks and non-blacks and has a side-effect profile comparable to placebo. Because of its

efficacy and safety in black patients, Bisoprolol Fumarate/-hydrochlorothiazide is an appropriate therapeutic option for

first-line therapy of hypertension in the black population.

--------------------------------------------------------------------------------------------------------

Angiology. 2009 Oct-Nov; 60(5):601-7. doi: 10.1177/0003319708324926. Epub 2008 Nov 21.

Papadopoulos DP1, Papademetriou V.

Low-dose fixed combination of Bisoprolol/hydrochlorothiazide as first line for hypertension: a review of the rationale

and clinical evidence.

Abstract: Essential hypertension is a heterogeneous multifactorial disease. Data from the National Health and Nutritional

Examination Survey and from the World Health Organization have clearly demonstrated that, worldwide, less than 30% of

hypertensive patients are adequately controlled by our currently accepted blood pressure goals. Although monotherapy is

often unable to achieve blood pressure goals, the use of fixed low-dose combination drugs as alternative treatment seems

to be related to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of

complementary mechanisms of antihypertensive effects. Indeed clinical trials have shown that initial low-dose combination

therapy is superior as compared with treatment by the stepped-care and the sequential monotherapy approach, while

recently, low-dose combination therapy for initial antihypertensive therapy instead of the stepped-care approach or of

sequential monotherapy has been recommended. This review summarizes the beneficial effect of low-dose bisoprolol/

hydrochlorothiazide combination in the treatment of patients with stage I and II hypertension

--------------------------------------------------------------------------------------------------------- Clin Cardiol. 1993 Oct; 16(10):732-6. ; Lewin AJ1, Lueg MC, Targum S, Cardenas P.

A clinical trial evaluating the 24-hour effects of bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination in patients

with mild to moderate hypertension.

Abstract: This study used 24-h ambulatory blood pressure (BP) monitoring to investigate the effectiveness of a novel low-

dose combination of bisoprolol/hydrochlorothiazide in adult patients with mild to moderate essential hypertension. Thirty-

six patients with stable mild to moderate hypertension (sitting diastolic BP 95-114 mmHg) after a placebo run-in phase

received oral bisoprolol/hydrochlorothiazide 5 mg/6.25 mg once daily for 4 weeks in a single-blind regimen. At office visits,

BP and pulse were measured with statistically significant reductions (p < 0.01) recorded after 2 and 4 weeks of treatment.

Twenty-four-h ambulatory BP monitoring at the completion of therapy revealed significant reductions (p < 0.01) in both

systolic and diastolic 24-h, daytime, and night-time BP, compared with the end of the placebo treatment phase. Systolic and

diastolic load were also reduced (p < 0.01). The combination was well tolerated, and overall quality-of-life questionnaire

scores indicated an improvement after bisoprolol/hydrochlorothiazide therapy (p = 0.02). No clinically significant changes

from baseline in laboratory parameters were observed; in particular, serum potassium was unchanged. This is the first

study to demonstrate the 24-h effectiveness of the bisoprolol/hydrochlorothiazide 5 mg/6.25 mg combination, using 24-h

ambulatory BP monitoring. In addition, antihypertensive therapy with low doses of bisoprolol/hydrochlorothiazide in

combination may improve tolerability



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ABSTRACTS Arq Bras Cardiol. 1998 Oct; 71(4):601-8.

Efficacy and tolerance of the bisoprolol/hydrochlorothiazide combination in arterial hypertension

Luna RL1, Oigman W, Ramirez JA, Mion D, Batlouni M, da Rocha JC, Feitosa GS, Castro I, Chaves Júnior Hde C, God EM, Maia

LN, Ortega KC, Raineri AM.

PURPOSE: Multicentre, open and non-controlled study to evaluate the efficacy and the tolerability of a low-dose

combination of two anti-hypertensive agents: a cardio selective beta-blocker, Bisoprolol (2.5 and 5.0 mg) with 6.25 mg of

hydrochlorothiazide.

METHODS: One hundred and six patients in the stage I and stage II of the systemic hypertension (mild to moderate) were

given the Bisoprolol/hydrochlorothiazide combination once daily and the diastolic and systolic blood pressures were

monitored during the 8-week trial.

RESULTS: The Bisoprolol/hydrochlorothiazide combination reduced the initial mean values of systolic and diastolic blood

pressures, respectively, from the 157.4 mmHg and 98.8 mmHg to 137.3 mmHg and 87.4 mmHg. At the end of the treatment

period, 61% of the patients normalized blood pressure values (< 90 mmHg) and 22.9% of them had responded to the

treatment, resulting in a total response rate (normalized + responsive) of 83.9% of cases. Adverse events were described

only in 18.9% of the patients and dizziness and headache were the most common.

There were no clinically significant changes on plasma levels of potassium, uric acid, glucose, or in the lipid profile.

CONCLUSION: The combination of low dosages of Bisoprolol and hydrochlorothiazide may be considered an effective, well

tolerated and rational alternative for the initial treatment of the patients with mild to moderate hypertension

--------------------------------------------------------------------------------------------------------- Clin Ther. 1993 Sep-Oct;15(5):779-87.

Low-dose bisoprolol/hydrochlorothiazide: an option in first-line, antihypertensive treatment.

Zachariah PK1, Messerli FH, Mroczek W.

Abstract

Two recent, multicenter, double-blind, placebo-controlled studies established the efficacy and safety of low-dose

bisoprolol/hydrochlorothiazide (HCTZ) in patients with mild to moderate essential hypertension. Bisoprolol, a cardio

selective beta-blocker, was used in a dose of 2.5 mg, 5 mg, or 10 mg. HCTZ was used at a dose of 6.25 mg. This low-dose

compound was developed to minimize dose-related adverse effects. The addition of HCTZ to each of the doses of bisoprolol

was compared with monotherapy and placebo. Results of both studies demonstrated that this once-a-day, low-dose option

effectively reduced sitting diastolic and systolic blood pressure measured at the end of the 24-hour dosing period. Drug-

related adverse effects, including those generally associated with traditional beta-blocker therapy, were infrequent in

individuals who received the low-dose bisoprolol/HCTZ regimen. Dose-related side effects were minimized because of the

low doses of the two agents used together. There were no significant changes in mean total cholesterol, triglycerides, or

serum glucose with bisoprolol/HCTZ 6.25 mg therapy versus placebo (analysis of variance statistical methods). The

incidence of treatment-induced hypokalaemia with bisoprolol/HCTZ 6.25 mg was not significant; uric acid elevations were

minimized, and the incidence of hyperuricemia was significantly (P < 0.01) less with bisoprolol/HCTZ 6.25 mg than with 25

mg of HCTZ. Once-a-day dosing with the low-dose agent controlled (defined as a sitting diastolic blood pressure < or = 90

mmHg and/or a decrease from baseline > or = 10 mmHg) blood pressure in up to 80% of patients for a full 24 hours after

dosing



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ABSTRACTS Trials. 2012 May 17; 13:59. doi: 10.1186/1745-6215-13-59.

Progress report on the first sub-Saharan Africa trial of newer versus older antihypertensive drugs in native black patients.

Odili AN1, Ezeala-Adikaibe B, Ndiaye MB, Anisiuba BC, Kamdem MM, Ijoma CK, Kaptue J, Boombhi HJ, Kolo PM, Shu EN,

Thijs L, Staessen JA, Omotoso BA, Kingue S, Ba SA, Lemogoum D, M'Buyamba-Kabangu JR, Ulasi II.

Abstract

BACKGROUND: The epidemic surge in hypertension in sub-Saharan Africa is not matched by clinical trials of

antihypertensive agents in Black patients recruited in this area of the world. We mounted the Newer versus Older

Antihypertensive agents in African Hypertensive patients (NOAAH) trial to compare, in native African patients, a single-pill

combination of newer drugs, not involving a diuretic, with a combination of older drugs including a diuretic.

METHODS: Patients aged 30 to 69 years with uncomplicated hypertension (140 to 179/90 to 109 mmHg) and ≤2 associated

risk factors are eligible. After a four week run-in period off treatment, 180 patients have to be randomized to once daily

Bisoprolol/hydrochlorothiazide 5/6.25 mg (R) or amlodipine/valsartan 5/160 mg (E).

To attain blood pressure <140/<90 mmHg during six months, the doses of Bisoprolol and amlodipine should be increased to

10 mg/day with the possible addition of up to 2 g/day α-methyldopa.

RESULTS: At the time of writing of this progress report, of 206 patients enrolled in the run-in period, 140 had been

randomized. At randomization, the R and E groups were similar (P ≥ 0.11) with respect to mean age (50.7 years), body mass

index (28.2 kg/m(2)), blood pressure (153.9/91.5 mmHg) and the proportions of women (53.6%) and treatment naïve

patients (72.7%). After randomization, in the R and E groups combined, blood pressure dropped by 18.2/10.1 mmHg,

19.4/11.2 mmHg, 22.4/12.2 mmHg and 25.8/15.2 mmHg at weeks two (n = 122), four (n = 109), eight (n = 57), and 12 (n =

49), respectively. The control rate was >65% already at two weeks. At 12 weeks, 12 patients (24.5%) had progressed to the

higher dose of R or E and/or had α-methyldopa added. Cohort analyses of 49 patients up to 12 weeks were confirmatory.

Only two patients dropped out of the study.

CONCLUSIONS: NOAAH (NCT01030458) demonstrated that blood pressure control can be achieved fast in Black patients

born and living in Africa with a simple regimen consisting of a single-pill combination of two antihypertensive agents.

NOAAH proves that randomized clinical trials of cardiovascular drugs in the indigenous populations of sub-Saharan Africa

are feasible

--------------------------------------------------------------------------------------------------------- J Clin Pharmacology. 1995 Feb; 35(2):182-8.

First-line therapy option with low-dose bisoprolol Fumarate and low-dose hydrochlorothiazide in patients with stage I

and stage II systemic hypertension.

Frishman WH1, Burris JF, Mroczek WJ, Weir MR, Alemayehu D, Simon JS, Chen SY, Bryzinski BS.

1Department of Medicine, Albert Einstein School of Medicine, Bronx, New York 10461, USA.

Abstract: This 30-center, randomized, double-blind, placebo-controlled, parallel-group study was designed to (1) establish

that 6.25 mg of hydrochlorothiazide (HCTZ) given once daily with 5 mg of Bisoprolol Fumarate can contribute to

antihypertensive effectiveness in patients with stage I and stage II (mild to moderate) systemic hypertension; and (2) assess

whether this formulation was more effective or possessed a safety advantage over standard monotherapy with Bisoprolol

or 25 mg of HCTZ. Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of

Bisoprolol 5 mg. Bisoprolol 5 mg/HCTZ 6.25 mg (B5/H6.25) produced significantly greater mean reductions from baseline in

sitting systolic and diastolic blood pressure (-15.8 mm Hg/-12.6 mm Hg) than Bisoprolol 5 mg alone (-10.0 mm Hg/-10.5 mm

Hg) and HCTZ 25 mg alone (-10.2 mm Hg/-8.5 mm Hg). A 73% response rate was achieved with the low-dose formulation

compared with 61% for the Bisoprolol 5 mg (B5) group and 47% for the HCTZ 25 mg (H25) group. B5/H6.25 was found to be

significantly more effective than B5 or H25 in all subgroups of patients, regardless of gender, race, age, or smoking history.

Antihypertensive effects were maintained during the 24-hour dosing interval. The incremental effectiveness of B5/H6.25

was not accompanied by an increase in the frequency or severity of adverse experiences; the incidence of adverse

experiences in the B5/H6.25 group was comparable to that in the placebo group. B5/H6.25 was shown to provide safety

advantages over H25, as shown by less hypokalaemia (< 1% with B5/H6.25 versus 6.5% with H25).

http://www.ncbi.nlm.nih.gov/pubmed

http://www.ncbi.nlm.nih.gov/pubmed?term=Frishman%20WH%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Burris%20JF%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Mroczek%20WJ%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Weir%20MR%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Alemayehu%20D%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Simon%20JS%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Chen%20SY%5BAuthor%5D&cauthor=true&cauthor_uid=7751430

http://www.ncbi.nlm.nih.gov/pubmed?term=Bryzinski%20BS%5BAuthor%5D&cauthor=true&cauthor_uid=7751430



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ABSTRACTS J Hypertens Suppl. 2002 Feb;20(1):S21-5.

Clinical results with bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg combination in systolic hypertension in the elderly.

Benetos A1, Adamopoulos C, Argyriadis P, Bean K, Consoli S, Safar M.

1IPC Center, Paris, France. [email protected]

Abstract: Hypertension in the elderly, especially systolic hypertension, has been recognized as a major cardiovascular risk

factor. Several international studies, using primarily diuretics and/or beta-blockers, have shown the benefits of

antihypertensive treatment in elderly patients in terms of cardiovascular morbidity and mortality reduction. However,

because the risk of side-effects is a major concern when treating the elderly, the use of low-dose combination treatments

may be of particular interest. A randomized, multicentre, double-blind, parallel group study was conducted to compare the

efficacy and safety of bisoprolol 2.5 mg/hydrochlorothiazide 6.25 mg (biso 2.5/HCTZ 6.25) (n = 84) versus amlodipine 5 mg

(n = 80) in subjects over 60years of age with isolated systolic hypertension. The effects of these two treatment strategies on

patients' quality of life were also assessed. After a two- to four-week placebo washout period, both drugs were

administered once daily and taken for 12 weeks. Blood pressure was measured 24 h after treatment administration. Systolic

blood pressure/diastolic blood pressure changes from baseline to week 12 were similar for both biso 2.5/HCTZ6.25 and

amlodipine (-20.0/-4.5 mmHg and -19.6/-2.4 mmHg, respectively). Overall adverse events for biso 2.5/HCTZ 6.25 and

amlodipine were 39% and 40%, respectively. Both treatments improved quality of life scores in the same way. This study

demonstrates comparable efficacy and tolerability of biso 2.5/HCTZ 6.25 and amlodipine. Low-dose combination of

bisoprolol and hydrochlorothiazide may be an appropriate alternative for elderly patients with systolic hypertension.

http://www.ncbi.nlm.nih.gov/pubmed/11996196

http://www.ncbi.nlm.nih.gov/pubmed?term=Benetos%20A%5BAuthor%5D&cauthor=true&cauthor_uid=11996196

http://www.ncbi.nlm.nih.gov/pubmed?term=Adamopoulos%20C%5BAuthor%5D&cauthor=true&cauthor_uid=11996196

http://www.ncbi.nlm.nih.gov/pubmed?term=Argyriadis%20P%5BAuthor%5D&cauthor=true&cauthor_uid=11996196

http://www.ncbi.nlm.nih.gov/pubmed?term=Bean%20K%5BAuthor%5D&cauthor=true&cauthor_uid=11996196

http://www.ncbi.nlm.nih.gov/pubmed?term=Consoli%20S%5BAuthor%5D&cauthor=true&cauthor_uid=11996196

http://www.ncbi.nlm.nih.gov/pubmed?term=Safar%20M%5BAuthor%5D&cauthor=true&cauthor_uid=11996196



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REFERENCES • BENETOS A, COSOLI S, SAFAVIANA, et al.: Efficacy, safety and effects on quality of life of

Bisoprolol/Hydrochlorothiazide versus Amlodipine in elderly patients with systolic hypertension. Am Heart J

2000; 140: e14.

• DE QUATTRO V, WEIR M. Bisoprolol Fumarate/Hydrochlorothiazide 6.25 mg: A new low-dose option for first-

line antihypertensive therapy. Advances in therapy 1993; 10 (5): 197-206.

• FRISHMAN WH, BRYZINSKI BS, COULSON LR, et al. A multifactorial trial design to assess combination therapy

in hypertension: Treatment with Bisoprolol and Hydrochlorothiazide. Arch Intern Med. 1994; 154: 1461-1468.

• FRISHMAN WH, BURRIS JF, MROCZEK WJ, et al. First-line therapy option with low-dose Bisoprolol Fumarate

and low-dose Hydrochlorothiazide in patients with stage I and stage II systemic hypertension. J Clin Pharmacol.

1995; 35: 182-188.

• FRISHMAN WH. ZIAC National Hypertension Trial Report. March 1996.

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H2-H10.

• JNC VI/The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and

Treatment of High Blood Pressure, NIH Publications 1997; No. 98-4080.

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5/Hydrochlorothiazide 6.25combination in patients with mild-to-moderate hypertension. Clin Cardiol. 1993; 16:

732-736.

• MOSER M, BLACK H. The role of combination therapy in the treatment of hypertension. Am J Hypertens

1998; 11: 73S-78S.

• NEUTEL JM, ROLF CN, VALENTINE SN, et al. Low-dose combination therapy as first line treatment of mild-to-

moderate hypertension: the efficacy and safety of Bisoprolol/6.25 HCTZ versus Amlodipine, Enalapril, and

placebo. Cardiovasc Rev Rep. 1996; 17: 33-45.

• PAPADEMETRIOU V, NEUTEL J, NARAVAN P, et al. Comparison of Bisoprolol and low dose

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CONTACTS

Contact us for any inquiries:

Country Director¦ +234 809 574 1998

Head of Sales & Marketing – Lagos territory¦ +234 809 574 1913

Medical Sales Rep. – Lagos Island¦ +234 809 574 1967

Medical Sales Rep. – Oyo State¦ +234 809 574 1972

Account & Administrative Coordinator¦ +234 809 574 1925

Swiss Rep. Office: +41 79 603 9042

[email protected]

www.theblackcedar.com

Registered Office

Blackcedar Pharmaceuticals Ltd.

18 Owode Street, Abule-Egba

Lagos, Nigeria

Representative Office

The Blackcedar GmbH

Hôtel-de-Ville 46

2300 La Chaux-de-Fonds

Switzerland

mailto:[email protected]

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